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• W4306174906 abstract "The recent COVID-19 pandemic has had a profound impact on global health. The importance of clinician awareness of the dermatological manifestations of the disease is paramount.1Genovese G. Moltrasio C. Berti E. Marzano A.V. Skin manifestations associated with COVID-19: current knowledge and future perspectives.Dermatology. 2021; 237: 1-12https://doi.org/10.1159/000512932Google Scholar In addition, the onset of vaccination programs to combat the disease is uncovering further cutaneous eruptions and systemic reaction patterns.2Temiz S.A. Abdelmaksoud A. Wollina U. et al.Cutaneous and Allergic reactions due to COVID-19 vaccinations: a review.J Cosmet Dermatol. 2022; 21: 4-12https://doi.org/10.1111/jocd.14613Google Scholar We present a case of cutaneous lupus in a patient with underlying secondary Sjögren’s syndrome following the Oxford–AstraZeneca COVID-19 vaccine (AZD1222), review the literature and highlight the potential for systemic lupus erythematosus or cutaneous lupus erythematosus (CLE) flare following COVID vaccination. A 51-year-old gentleman with a diagnosis of systemic lupus erythematosus (positive dsDNA [anti double stranded DNA] and ANA titers) with overlapping features of Sjögren’s disease (parotid swelling, Ro and La antibody positivity, recurrent pleuropericardial effusions, and bronchiectasis) managed with hydroxychloroquine and azathioprine presented to dermatology in April 2021 with a widespread pruritic eruption. Onset was 1 week after receiving the Oxford–AstraZeneca COVID-19 vaccine (AZD1222) (January 2021), with subsequent exacerbation 4 days after the second dose, 2 months later; managed by his family physician with prednisolone 30 mg for 5 days. The patient was not started on any new medications prior to the onset of the eruption and had not displayed cutaneous lupus features in the past. On presentation, he exhibited indurated, flat-topped papular lesions on the scalp, dorsal hands, ears and erythematous, polycyclic, annular lesions on the arms, back, scalp and trunk suspicious for discoid, and subacute CLE, respectively (Fig 1, A-D). Palmar perniosis was noted. Punch biopsies from the back and dorsa of the hand demonstrated features consistent with CLE including vacuolar interface dermatitis with pigmentary incontinence, apoptotic keratinocytes, and an inflammatory lymphocytic infiltrate in the superficial dermis (Fig 2, A and B). Direct immunofluorescence from a non–sun-exposed site on the back revealed immunoglobulin G anti-nuclear antibodies throughout the epidermis (red) with C3 deposition (green) in the basement membrane (Fig 3, A). An autoimmune screen revealed positive ANA titers, as previously. Anti-Ro/SSA and anti-Sm antibodies (anti Smith antibody) were positive, in keeping with the patient’s history of Sjögren’s-like features, as well as a chronically raised erythrocyte sedimentation rate and neutropenia. His renal function was unremarkable. He reported no systemic symptoms.Fig 3A, direct immunofluorescence reveals immunoglobulin G antibodies throughout the epidermis (red) with C3 deposition (green) in the basement membrane consistent with connective tissue disease. B, postulated mechanism of vaccine-induced cutaneous lupus. COVID-19 vaccines trigger innate sensors which lead to type 1 interferon secretion, resulting in the activation of cytokine and chemokine cascades. T-cell activation ensues followed by a lichenoid tissue reaction. TLRs, Toll-like receptorsView Large Image Figure ViewerDownload Hi-res image Download (PPT) A diagnosis of Oxford-AstraZeneca COVID-19 vaccine (AZD1222) induced CLE was made in view of the clinical features, histology, direct immunofluorescence, and antibody profile. Hydroxychloroquine dosage was increased from 200 mg to 400 mg and azathioprine from 100 mg to 150 mg daily. At 6 months, the acute eruption had resolved leaving widespread post-inflammatory hypopigmentation with areas of vitiligo-like post inflammatory depigmentation (Fig 1, E-G). At further follow-up there is evidence for repigmentation within some of the lesions. Cutaneous eruptions following COVID-19 infection are not uncommon. Although the exact incidence is yet to be ascertained, cutaneous manifestations have been reported in up to 20% of cases3Recalcati S. Cutaneous manifestations in COVID-19: a first perspective.J Eur Acad Dermatol Venereol. 2020; 34: e212-e213https://doi.org/10.1111/jdv.16387Google Scholar and can encompass a wide range of morphologies including urticarial, morbilliform, papulovesicular, chilblain-like, livedoid, and vasculitic.1Genovese G. Moltrasio C. Berti E. Marzano A.V. Skin manifestations associated with COVID-19: current knowledge and future perspectives.Dermatology. 2021; 237: 1-12https://doi.org/10.1159/000512932Google Scholar Far less commonly (<0.5% of cases), a wide range of cutaneous eruptions have also been reported post-COVID-19 vaccination but these are more often associated with the mRNA vaccines (BNT162b2 Pfizer-BioNTech and mRNA-1273 Moderna). Pityriasis rosea, urticaria, and chilblain-like lesions are the most frequently observed morphologies (0.1% to 0.4% of cases); whereas, morbilliform and petechial eruptions (<0.1% of cases) have been associated with adenoviral vector vaccines.2Temiz S.A. Abdelmaksoud A. Wollina U. et al.Cutaneous and Allergic reactions due to COVID-19 vaccinations: a review.J Cosmet Dermatol. 2022; 21: 4-12https://doi.org/10.1111/jocd.14613Google Scholar CLE following COVID-19 vaccination is uncommon. Our case is only the second reported after exposure to the Oxford–AstraZeneca adenoviral vaccine (AZD1222),4Kreuter A. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Transition of cutaneous into systemic lupus erythematosus following adenoviral vector-based SARS-CoV-2 vaccination.J Eur Acad Dermatol Venereol. 2021; 35: e733-e735https://doi.org/10.1111/jdv.17514Google Scholar with the majority of remaining cases reported after exposure to the Pfizer mRNA vaccine (BNT162b2).4Kreuter A. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Transition of cutaneous into systemic lupus erythematosus following adenoviral vector-based SARS-CoV-2 vaccination.J Eur Acad Dermatol Venereol. 2021; 35: e733-e735https://doi.org/10.1111/jdv.17514Google Scholar, 5Gambichler T. Scholl L. Dickel H. Ocker L. Stranzenbach R. Prompt onset of Rowell's syndrome following the first BNT162b2 SARS-CoV-2 vaccination.J Eur Acad Dermatol Venereol. 2021; 35: e415-e416https://doi.org/10.1111/jdv.17225Google Scholar, 6Niebel D. Ralser-Isselstein V. Jaschke K. Braegelmann C. Bieber T. Wenzel J. Exacerbation of subacute cutaneous lupus erythematosus following vaccination with BNT162b2 mRNA vaccine.Dermatol Ther. 2021; 34: e15017https://doi.org/10.1111/dth.15017Google Scholar, 7Kreuter A. Licciardi-Fernandez M.J. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA-based or adenoviral vector-based SARS-CoV-2 vaccination.Clin Exp Dermatol. 2022; 47: 161-163https://doi.org/10.1111/ced.14858Google Scholar, 8Rechtien L. Erfurt-Berge C. Sticherling M. SCLE manifestation after mRNA COVID-19 vaccination.J Eur Acad Dermatol Venereol. 2022; 36: e261-e263https://doi.org/10.1111/jdv.17895Google Scholar, 9Rose C. Apgar R. Green M. Cutaneous lupus-erythematosus-like reaction arising after COVID-19 vaccination.J Cutan Pathol. 2022; 49: 943-946https://doi.org/10.1111/cup.14281Google Scholar, 10Liu V. Messenger N.B. New-onset cutaneous lupus erythematosus after the COVID-19 vaccine.Dermatol Online J. 2021; 27https://doi.org/10.5070/D3271156093Google Scholar, 11Zengarini C. Pileri A. Salamone F.P. Piraccini B.M. Vitale G. La Placa M. Subacute cutaneous lupus erythematosus induction after SARS-CoV-2 vaccine in a patient with primary biliary cholangitis.J Eur Acad Dermatol Venereol. 2022; 36: e179-e180https://doi.org/10.1111/jdv.17827Google Scholar, 12Niebel D. Wilhelmi J. De Vos L. et al.Annular plaques mimicking Rowell's syndrome in the course of coronavirus disease 2019 mRNA vaccines: an overlooked phenomenon?.J Dermatol. 2022; 49: 151-156https://doi.org/10.1111/1346-8138.16210Google Scholar The summary of CLE eruptions occurring post-COVID vaccination is summarized in Table I. The postulated mechanism behind CLE eruption following COVID-19 vaccination involves increased Type 1 interferon (IFN) secretion. In the pathogenesis of cutaneous lupus this is triggered by the binding of immune complexes to toll-like receptors on dendritic cells. Both mRNA and adenoviral COVID-19 vaccines trigger innate sensors leading to Type 1 IFN secretion,13Teijaro J.R. Farber D.L. COVID-19 vaccines: modes of immune activation and future challenges.Nat Rev Immunol. 2021; 21: 195-197https://doi.org/10.1038/s41577-021-00526-xGoogle Scholar resulting in cytokine and chemokine cascades, T-cell activation, and a lichenoid tissue reaction (Fig 3, B). Interestingly, the majority of cases are associated with anti-Ro and anti-La antibodies, which are often newly positive.4Kreuter A. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Transition of cutaneous into systemic lupus erythematosus following adenoviral vector-based SARS-CoV-2 vaccination.J Eur Acad Dermatol Venereol. 2021; 35: e733-e735https://doi.org/10.1111/jdv.17514Google Scholar,7Kreuter A. Licciardi-Fernandez M.J. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA-based or adenoviral vector-based SARS-CoV-2 vaccination.Clin Exp Dermatol. 2022; 47: 161-163https://doi.org/10.1111/ced.14858Google Scholar,8Rechtien L. Erfurt-Berge C. Sticherling M. SCLE manifestation after mRNA COVID-19 vaccination.J Eur Acad Dermatol Venereol. 2022; 36: e261-e263https://doi.org/10.1111/jdv.17895Google Scholar,10Liu V. Messenger N.B. New-onset cutaneous lupus erythematosus after the COVID-19 vaccine.Dermatol Online J. 2021; 27https://doi.org/10.5070/D3271156093Google Scholar,11Zengarini C. Pileri A. Salamone F.P. Piraccini B.M. Vitale G. La Placa M. Subacute cutaneous lupus erythematosus induction after SARS-CoV-2 vaccine in a patient with primary biliary cholangitis.J Eur Acad Dermatol Venereol. 2022; 36: e179-e180https://doi.org/10.1111/jdv.17827Google Scholar Anti-Ro antibodies are encountered in up to 70% of non-vaccine associated subacute CLE cases. Furthermore, anti-Ro and/or anti-La positivity is also associated with an increased IFN signature.14Wither J. Johnson S.R. Liu T. et al.Presence of an interferon signature in individuals who are anti-nuclear antibody positive lacking a systemic autoimmune rheumatic disease diagnosis.Arthritis Res Ther. 2017; 19: 41https://doi.org/10.1186/s13075-017-1243-yGoogle ScholarTable ISummary of reported cutaneous lupus reactions occurring post-COVID vaccinationPatientAge (years)SexAutoimmune disease historyCOVID vaccine typeCLE subtypeInduction or exacerbation of CLEOnset of skin lesions post-vaccine (days)Antibody profileReference174FNilmRNA (BNT162b2)SCLEInduction1ANA (1:640)Anti-Ro, anti-LaGambichler et al5Gambichler T. Scholl L. Dickel H. Ocker L. Stranzenbach R. Prompt onset of Rowell's syndrome following the first BNT162b2 SARS-CoV-2 vaccination.J Eur Acad Dermatol Venereol. 2021; 35: e415-e416https://doi.org/10.1111/jdv.17225Google Scholar273FSCLEmRNA (BNT162b2)SCLEExacerbation10Anti-RoNiebel et al6Niebel D. Ralser-Isselstein V. Jaschke K. Braegelmann C. Bieber T. Wenzel J. Exacerbation of subacute cutaneous lupus erythematosus following vaccination with BNT162b2 mRNA vaccine.Dermatol Ther. 2021; 34: e15017https://doi.org/10.1111/dth.15017Google Scholar362FSCLEAdenoviral (AZD1222)SCLEExacerbation and systemic transformation10ANA (1:640) anti-Ro, anti-LaKreuter et al4Kreuter A. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Transition of cutaneous into systemic lupus erythematosus following adenoviral vector-based SARS-CoV-2 vaccination.J Eur Acad Dermatol Venereol. 2021; 35: e733-e735https://doi.org/10.1111/jdv.17514Google Scholar454FSCLEmRNA-1273 (Moderna)SCLEExacerbation4ANA (1:1280) anti-dsDNA, anti-SmJoseph et al15Joseph A.K. Chong B.F. Subacute cutaneous lupus erythematosus flare triggered by COVID-19 vaccine.Dermatologic Therapy. 2021; 34: e15114https://doi.org/10.1111/dth.15114Google Scholar570MNilmRNA (BNT162b2)SCLEInduction10 wkANA (1:540) anti-RoLiu et al10Liu V. Messenger N.B. New-onset cutaneous lupus erythematosus after the COVID-19 vaccine.Dermatol Online J. 2021; 27https://doi.org/10.5070/D3271156093Google Scholar679MNilmRNA (BNT162b2)SCLEInduction10ANA (1:320) anti-Ro, anti-LaKreuter et al7Kreuter A. Licciardi-Fernandez M.J. Burmann S.N. Burkert B. Oellig F. Michalowitz A.L. Induction and exacerbation of subacute cutaneous lupus erythematosus following mRNA-based or adenoviral vector-based SARS-CoV-2 vaccination.Clin Exp Dermatol. 2022; 47: 161-163https://doi.org/10.1111/ced.14858Google Scholar730FPrimary biliary cholangitismRNA (BNT162b2)SCLEInduction10Anti-dsDNA, anti-Sm, anti-nRNP anti-Ro, anti-LaZengarini et al11Zengarini C. Pileri A. Salamone F.P. Piraccini B.M. Vitale G. La Placa M. Subacute cutaneous lupus erythematosus induction after SARS-CoV-2 vaccine in a patient with primary biliary cholangitis.J Eur Acad Dermatol Venereol. 2022; 36: e179-e180https://doi.org/10.1111/jdv.17827Google Scholar841MMCTDmRNA (BNT162b2)RSInduction4Speckled ANANiebel et al12Niebel D. Wilhelmi J. De Vos L. et al.Annular plaques mimicking Rowell's syndrome in the course of coronavirus disease 2019 mRNA vaccines: an overlooked phenomenon?.J Dermatol. 2022; 49: 151-156https://doi.org/10.1111/1346-8138.16210Google Scholar922FHypothyroidismmRNA-1273 (Moderna)Drug-induced SCLE mimicking RSInduction10ANA (1:80)Niebel et al12Niebel D. Wilhelmi J. De Vos L. et al.Annular plaques mimicking Rowell's syndrome in the course of coronavirus disease 2019 mRNA vaccines: an overlooked phenomenon?.J Dermatol. 2022; 49: 151-156https://doi.org/10.1111/1346-8138.16210Google Scholar1024FSLEmRNA (BNT162b2)SCLEInduction14Anti-dsDNA, anti-Sm, anti-histoneLaRechtien et al8Rechtien L. Erfurt-Berge C. Sticherling M. SCLE manifestation after mRNA COVID-19 vaccination.J Eur Acad Dermatol Venereol. 2022; 36: e261-e263https://doi.org/10.1111/jdv.17895Google Scholar1133FNilmRNA (BNT162b2)SCLEInduction1NilRose et al9Rose C. Apgar R. Green M. Cutaneous lupus-erythematosus-like reaction arising after COVID-19 vaccination.J Cutan Pathol. 2022; 49: 943-946https://doi.org/10.1111/cup.14281Google Scholar1251MSLE and Sjogren’s overlapAdenoviral (AZD1222)DLE and SCLEInduction7ANA (1:1280)Anti-dsDNA, anti-Sm anti-Ro, anti-LaPresent caseANA, Antinuclear antibody; Anti-dsDNA, anti-double stranded DNA; anti-Sm, anti-Smith antibody; F, Female; M, Male; MCTD, mixed connective tissue disease; SCLE, subacute cutaneous lupus erythematosus; SLE, systemic lupus erythematosus; RS, Rowell’s syndrome. Open table in a new tab ANA, Antinuclear antibody; Anti-dsDNA, anti-double stranded DNA; anti-Sm, anti-Smith antibody; F, Female; M, Male; MCTD, mixed connective tissue disease; SCLE, subacute cutaneous lupus erythematosus; SLE, systemic lupus erythematosus; RS, Rowell’s syndrome. The vitiligo-like depigmentation is an unusual and interesting feature with some evidence of repigmentation at follow-up. Cases of vitiligo post-COVID vaccination have been reported in the literature16Herzum A. Micalizzi C. Molle M.F. Parodi A. New-onset vitiligo following COVID-19 disease.Ski Heal Dis. 2022; 2: e86https://doi.org/10.1002/ski2.86Google Scholar and may again be related to type 1 IFN production which is also an early phase in vitiligo pathogenesis.17Bertolotti A. Boniface K. Vergier B. et al.Type I interferon signature in the initiation of the immune response in vitiligo.Pigment Cell Melanoma Res. 2014; 27: 398-407https://doi.org/10.1111/pcmr.12219Google Scholar In summary, we present a case of CLE following the Oxford–AstraZeneca COVID-19 vaccine (AZD1222) with subsequent vitiligo-like depigmentation. Decisions as to further vaccination were made on a personalized risk benefit analysis and a subsequent dose of Pfizer mRNA vaccine (BNT162b2) was well tolerated. None disclosed." @default.
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• W4306174906 title "Cutaneous lupus erythematosus flare with vitiligo-like depigmentation following the AstraZeneca COVID vaccine" @default.
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